Son K, Huang L
Department of Pharmacology, University of Pittsburgh School of Medicine, PA 15261.
Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12669-72. doi: 10.1073/pnas.91.26.12669.
Human ovarian carcinoma cells (line 2008) grown as subcutaneous solid tumor in the severe combined immunodeficient mouse can be transfected by directly injecting a plasmid DNA-liposome complex into the tumor (in situ lipofection). The level of reporter gene expression in the tumor cells was significantly elevated if the animal received a single i.p. injection of cisplatin 1 week before the lipofection. Sensitization of the tumor for lipofection peaked 1 week after cisplatin injection and declined thereafter. Cells exposed to low concentration of cisplatin in vitro for four to five doubling times also showed elevated sensitivity for lipofection in vitro. Cisplatin was the only anticancer drug tested that exhibited this activity. These results suggest a sequential combinational gene therapy protocol with cisplatin for the ovarian carcinoma.
作为皮下实体瘤在严重联合免疫缺陷小鼠体内生长的人卵巢癌细胞（2008系），可通过将质粒DNA-脂质体复合物直接注射到肿瘤中（原位脂质转染）进行转染。如果动物在脂质转染前1周接受一次腹腔注射顺铂，肿瘤细胞中报告基因的表达水平会显著升高。肿瘤对脂质转染的敏感性在顺铂注射后1周达到峰值，此后下降。在体外暴露于低浓度顺铂四至五个倍增时间的细胞，在体外对脂质转染也表现出更高的敏感性。顺铂是所测试的唯一具有这种活性的抗癌药物。这些结果提示了一种顺铂用于卵巢癌的序贯联合基因治疗方案。
